Abstract
In the course of human immunodeficiency virus type 1 (HIV-1) infection, patients develop a strong and persistent immune response characterized by the production of HIV-specific antibodies. The aim of our study was to analyze the appearance of autologous and heterologous neutralizing antibodies in the sera of HIV-infected individuals. For this purpose, primary strains have been isolated from 18 HIV-1-infected subjects prior to seroconversion (in one case) or within 1 to 8 months after seroconversion. Sera, collected at the same time as the virus was isolated and at various times after isolation, have been analyzed for their ability to neutralize the autologous primary strains isolated early after infection, heterologous primary isolates, and cell-line adapted strains. Our neutralization assay, which combines serial dilutions of virus and serial dilutions of sera, is based on the determination of the serum dilution at which a fixed reduction in virus titer (90%) occurs. We have shown that (i) we could not detect autologous neutralizing antibodies in sera collected at the same time as we isolated viruses; (ii) we detected neutralizing antibodies against the autologous strains about 1 year after seroconversion, occasionally after 8 months, but sera were not always available to exclude the presence of neutralizing antibodies at earlier times; (iii) after 1 year, the neutralization response was highly specific to virus present during the early phase of HIV infection; and (iv) heterologous neutralization of primary isolates was detected later (after about 2 years). These results reveal the enormous diversity of neutralization determinants on primary isolates as well as a temporal evolution of the humoral response generating cross-reactive neutralizing antibodies.
Full Text
The Full Text of this article is available as a PDF (140.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ait-Khaled M., Emery V. C. Sequence variation within the human immunodeficiency virus V3 loop at seroconversion. J Med Virol. 1993 Dec;41(4):270–274. doi: 10.1002/jmv.1890410403. [DOI] [PubMed] [Google Scholar]
- Arendrup M., Akerblom L., Heegaard P. M., Nielsen J. O., Hansen J. E. The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies. Arch Virol. 1995;140(4):655–670. doi: 10.1007/BF01309956. [DOI] [PubMed] [Google Scholar]
- Ariyoshi K., Harwood E., Chiengsong-Popov R., Weber J. Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies? Lancet. 1992 Nov 21;340(8830):1257–1258. doi: 10.1016/0140-6736(92)92953-d. [DOI] [PubMed] [Google Scholar]
- Baldinotti F., Matteucci D., Mazzetti P., Giannelli C., Bandecchi P., Tozzini F., Bendinelli M. Serum neutralization of feline immunodeficiency virus is markedly dependent on passage history of the virus and host system. J Virol. 1994 Jul;68(7):4572–4579. doi: 10.1128/jvi.68.7.4572-4579.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Björling E., Scarlatti G., von Gegerfelt A., Albert J., Biberfeld G., Chiodi F., Norrby E., Fenyö E. M. Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection. Virology. 1993 Mar;193(1):528–530. doi: 10.1006/viro.1993.1160. [DOI] [PubMed] [Google Scholar]
- Bou-Habib D. C., Roderiquez G., Oravecz T., Berman P. W., Lusso P., Norcross M. A. Cryptic nature of envelope V3 region epitopes protects primary monocytotropic human immunodeficiency virus type 1 from antibody neutralization. J Virol. 1994 Sep;68(9):6006–6013. doi: 10.1128/jvi.68.9.6006-6013.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med. 1995 Jan 26;332(4):201–208. doi: 10.1056/NEJM199501263320401. [DOI] [PubMed] [Google Scholar]
- Cohen J. Jitters jeopardize AIDS vaccine trials. Science. 1993 Nov 12;262(5136):980–981. doi: 10.1126/science.8235635. [DOI] [PubMed] [Google Scholar]
- Delwart E. L., Sheppard H. W., Walker B. D., Goudsmit J., Mullins J. I. Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays. J Virol. 1994 Oct;68(10):6672–6683. doi: 10.1128/jvi.68.10.6672-6683.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., Di Marzio P., Marmon S., Sutton R. E., Hill C. M. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661–666. doi: 10.1038/381661a0. [DOI] [PubMed] [Google Scholar]
- Dragic T., Litwin V., Allaway G. P., Martin S. R., Huang Y., Nagashima K. A., Cayanan C., Maddon P. J., Koup R. A., Moore J. P. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun 20;381(6584):667–673. doi: 10.1038/381667a0. [DOI] [PubMed] [Google Scholar]
- Feng Y., Broder C. C., Kennedy P. E., Berger E. A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996 May 10;272(5263):872–877. doi: 10.1126/science.272.5263.872. [DOI] [PubMed] [Google Scholar]
- Gallo D., Kimpton J. S., Dailey P. J. Comparative studies on use of fresh and frozen peripheral blood lymphocyte specimens for isolation of human immunodeficiency virus and effects of cell lysis on isolation efficiency. J Clin Microbiol. 1987 Jul;25(7):1291–1294. doi: 10.1128/jcm.25.7.1291-1294.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Golding H., D'Souza M. P., Bradac J., Mathieson B., Fast P. Neutralization of HIV-1. AIDS Res Hum Retroviruses. 1994 Jun;10(6):633–643. doi: 10.1089/aid.1994.10.633. [DOI] [PubMed] [Google Scholar]
- Hariharan K., Nara P. L., Shabazz L. A., McCutchan J. A., Kang C. Y. Analysis of B cell repertoire specific to the neutralizing epitopes of glycoprotein 120 in HIV-infected individuals. AIDS Res Hum Retroviruses. 1994 Dec;10(12):1629–1637. doi: 10.1089/aid.1994.10.1629. [DOI] [PubMed] [Google Scholar]
- Heath S. L., Tew J. G., Tew J. G., Szakal A. K., Burton G. F. Follicular dendritic cells and human immunodeficiency virus infectivity. Nature. 1995 Oct 26;377(6551):740–744. doi: 10.1038/377740a0. [DOI] [PubMed] [Google Scholar]
- Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
- Hogervorst E., Jurriaans S., de Wolf F., van Wijk A., Wiersma A., Valk M., Roos M., van Gemen B., Coutinho R., Miedema F. Predictors for non- and slow progression in human immunodeficiency virus (HIV) type 1 infection: low viral RNA copy numbers in serum and maintenance of high HIV-1 p24-specific but not V3-specific antibody levels. J Infect Dis. 1995 Apr;171(4):811–821. doi: 10.1093/infdis/171.4.811. [DOI] [PubMed] [Google Scholar]
- Holmbäck K., Kusk P., Hulgaard E. F., Bugge T. H., Scheibel E., Lindhardt B. O. Autologous antibody response against the principal neutralizing domain of human immunodeficiency virus type 1 isolated from infected humans. J Virol. 1993 Mar;67(3):1612–1619. doi: 10.1128/jvi.67.3.1612-1619.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Javaherian K., Langlois A. J., McDanal C., Ross K. L., Eckler L. I., Jellis C. L., Profy A. T., Rusche J. R., Bolognesi D. P., Putney S. D. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768–6772. doi: 10.1073/pnas.86.17.6768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karlsson G. B., Gao F., Robinson J., Hahn B., Sodroski J. Increased envelope spike density and stability are not required for the neutralization resistance of primary human immunodeficiency viruses. J Virol. 1996 Sep;70(9):6136–6142. doi: 10.1128/jvi.70.9.6136-6142.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klasse P. J., Moore J. P. Quantitative model of antibody- and soluble CD4-mediated neutralization of primary isolates and T-cell line-adapted strains of human immunodeficiency virus type 1. J Virol. 1996 Jun;70(6):3668–3677. doi: 10.1128/jvi.70.6.3668-3677.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lombardi S., Garzelli C., Pistello M., Massi C., Matteucci D., Baldinotti F., Cammarota G., da Prato L., Bandecchi P., Tozzini F. A neutralizing antibody-inducing peptide of the V3 domain of feline immunodeficiency virus envelope glycoprotein does not induce protective immunity. J Virol. 1994 Dec;68(12):8374–8379. doi: 10.1128/jvi.68.12.8374-8379.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackewicz C. E., Yang L. C., Lifson J. D., Levy J. A. Non-cytolytic CD8 T-cell anti-HIV responses in primary HIV-1 infection. Lancet. 1994 Dec 17;344(8938):1671–1673. doi: 10.1016/s0140-6736(94)90459-6. [DOI] [PubMed] [Google Scholar]
- Mascola J. R., Louwagie J., McCutchan F. E., Fischer C. L., Hegerich P. A., Wagner K. F., Fowler A. K., McNeil J. G., Burke D. S. Two antigenically distinct subtypes of human immunodeficiency virus type 1: viral genotype predicts neutralization serotype. J Infect Dis. 1994 Jan;169(1):48–54. doi: 10.1093/infdis/169.1.48. [DOI] [PubMed] [Google Scholar]
- McKeating J. A., Bennett J., Zolla-Pazner S., Schutten M., Ashelford S., Brown A. L., Balfe P. Resistance of a human serum-selected human immunodeficiency virus type 1 escape mutant to neutralization by CD4 binding site monoclonal antibodies is conferred by a single amino acid change in gp120. J Virol. 1993 Sep;67(9):5216–5225. doi: 10.1128/jvi.67.9.5216-5225.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKnight A., Clapham P. R., Goudsmit J., Cheingsong-Popov R., Weber J. N., Weiss R. A. Development of HIV-1 group-specific neutralizing antibodies after seroconversion. AIDS. 1992 Aug;6(8):799–802. doi: 10.1097/00002030-199208000-00005. [DOI] [PubMed] [Google Scholar]
- Milich L., Margolin B., Swanstrom R. V3 loop of the human immunodeficiency virus type 1 Env protein: interpreting sequence variability. J Virol. 1993 Sep;67(9):5623–5634. doi: 10.1128/jvi.67.9.5623-5634.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montefiori D. C., Pantaleo G., Fink L. M., Zhou J. T., Zhou J. Y., Bilska M., Miralles G. D., Fauci A. S. Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors. J Infect Dis. 1996 Jan;173(1):60–67. doi: 10.1093/infdis/173.1.60. [DOI] [PubMed] [Google Scholar]
- Moog C., Spenlehauer C., Fleury H., Heshmati F., Saragosti S., Letourneur F., Kirn A., Aubertin A. M. Neutralization of primary human immunodeficiency virus type 1 isolates: a study of parameters implicated in neutralization in vitro. AIDS Res Hum Retroviruses. 1997 Jan 1;13(1):19–27. doi: 10.1089/aid.1997.13.19. [DOI] [PubMed] [Google Scholar]
- Moog C., Wick A., Le Ber P., Kirn A., Aubertin A. M. Bicyclic imidazo derivatives, a new class of highly selective inhibitors for the human immunodeficiency virus type 1. Antiviral Res. 1994 Aug;24(4):275–288. doi: 10.1016/0166-3542(94)90075-2. [DOI] [PubMed] [Google Scholar]
- Moore J. P., Cao Y., Ho D. D., Koup R. A. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J Virol. 1994 Aug;68(8):5142–5155. doi: 10.1128/jvi.68.8.5142-5155.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore J. P., Cao Y., Leu J., Qin L., Korber B., Ho D. D. Inter- and intraclade neutralization of human immunodeficiency virus type 1: genetic clades do not correspond to neutralization serotypes but partially correspond to gp120 antigenic serotypes. J Virol. 1996 Jan;70(1):427–444. doi: 10.1128/jvi.70.1.427-444.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore J. P., Cao Y., Qing L., Sattentau Q. J., Pyati J., Koduri R., Robinson J., Barbas C. F., 3rd, Burton D. R., Ho D. D. Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120. J Virol. 1995 Jan;69(1):101–109. doi: 10.1128/jvi.69.1.101-109.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore J. P., Ho D. D. Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J Virol. 1993 Feb;67(2):863–875. doi: 10.1128/jvi.67.2.863-875.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore J. P., Ho D. D. HIV-1 neutralization: the consequences of viral adaptation to growth on transformed T cells. AIDS. 1995;9 (Suppl A):S117–S136. [PubMed] [Google Scholar]
- Nyambi P. N., Nkengasong J., Lewi P., Andries K., Janssens W., Fransen K., Heyndrickx L., Piot P., van der Groen G. Multivariate analysis of human immunodeficiency virus type 1 neutralization data. J Virol. 1996 Sep;70(9):6235–6243. doi: 10.1128/jvi.70.9.6235-6243.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paul W. E. Can the immune response control HIV infection? Cell. 1995 Jul 28;82(2):177–182. doi: 10.1016/0092-8674(95)90304-6. [DOI] [PubMed] [Google Scholar]
- Pellegrin I., Legrand E., Neau D., Bonot P., Masquelier B., Pellegrin J. L., Ragnaud J. M., Bernard N., Fleury H. J. Kinetics of appearance of neutralizing antibodies in 12 patients with primary or recent HIV-1 infection and relationship with plasma and cellular viral loads. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Apr 15;11(5):438–447. doi: 10.1097/00042560-199604150-00003. [DOI] [PubMed] [Google Scholar]
- Planz O., Seiler P., Hengartner H., Zinkernagel R. M. Specific cytotoxic T cells eliminate B cells producing virus-neutralizing antibodies [corrected]. Nature. 1996 Aug 22;382(6593):726–729. doi: 10.1038/382726a0. [DOI] [PubMed] [Google Scholar]
- Poignard P., Klasse P. J., Sattentau Q. J. Antibody neutralization of HIV-1. Immunol Today. 1996 May;17(5):239–246. doi: 10.1016/0167-5699(96)10007-4. [DOI] [PubMed] [Google Scholar]
- Robert-Guroff M., Brown M., Gallo R. C. HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex. Nature. 1985 Jul 4;316(6023):72–74. doi: 10.1038/316072a0. [DOI] [PubMed] [Google Scholar]
- Sankalé J. L., de la Tour R. S., Renjifo B., Siby T., Mboup S., Marlink R. G., Essex M. E., Kanki P. J. Intrapatient variability of the human immunodeficiency virus type 2 envelope V3 loop. AIDS Res Hum Retroviruses. 1995 May;11(5):617–623. doi: 10.1089/aid.1995.11.617. [DOI] [PubMed] [Google Scholar]
- Sattentau Q. J., Moore J. P. Human immunodeficiency virus type 1 neutralization is determined by epitope exposure on the gp120 oligomer. J Exp Med. 1995 Jul 1;182(1):185–196. doi: 10.1084/jem.182.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scarlatti G., Albert J., Rossi P., Hodara V., Biraghi P., Muggiasca L., Fenyö E. M. Mother-to-child transmission of human immunodeficiency virus type 1: correlation with neutralizing antibodies against primary isolates. J Infect Dis. 1993 Jul;168(1):207–210. doi: 10.1093/infdis/168.1.207. [DOI] [PubMed] [Google Scholar]
- Scarlatti G., Leitner T., Hodara V., Jansson M., Karlsson A., Wahlberg J., Rossi P., Uhlén M., Fenyö E. M., Albert J. Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS. Immunol Lett. 1996 Jun;51(1-2):23–28. doi: 10.1016/0165-2478(96)02550-3. [DOI] [PubMed] [Google Scholar]
- Schlienger K., Montefiori D. C., Mancini M., Rivière Y., Tiollais P., Michel M. L. Vaccine-induced neutralizing antibodies directed in part to the simian immunodeficiency virus (SIV) V2 domain were unable to protect rhesus monkeys from SIV experimental challenge. J Virol. 1994 Oct;68(10):6578–6588. doi: 10.1128/jvi.68.10.6578-6588.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schreiber M., Petersen H., Wachsmuth C., Müller H., Hufert F. T., Schmitz H. Antibodies of symptomatic human immunodeficiency virus type 1-infected individuals are directed to the V3 domain of noninfectious and not of infectious virions present in autologous serum. J Virol. 1994 Jun;68(6):3908–3916. doi: 10.1128/jvi.68.6.3908-3916.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spira A. I., Ho D. D. Effect of different donor cells on human immunodeficiency virus type 1 replication and selection in vitro. J Virol. 1995 Jan;69(1):422–429. doi: 10.1128/jvi.69.1.422-429.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sullivan N., Sun Y., Li J., Hofmann W., Sodroski J. Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates. J Virol. 1995 Jul;69(7):4413–4422. doi: 10.1128/jvi.69.7.4413-4422.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tamalet C., Simon F., Dhiver C., Matheron S., de Micco P., Gastao J. A., Brun-Vézinet F. Autologous neutralizing antibodies and viral load in HIV-2-infected individuals. AIDS. 1995 Jan;9(1):90–91. [PubMed] [Google Scholar]
- Tsang M. L., Evans L. A., McQueen P., Hurren L., Byrne C., Penny R., Tindall B., Cooper D. A. Neutralizing antibodies against sequential autologous human immunodeficiency virus type 1 isolates after seroconversion. J Infect Dis. 1994 Nov;170(5):1141–1147. doi: 10.1093/infdis/170.5.1141. [DOI] [PubMed] [Google Scholar]
- Vancott T. C., Polonis V. R., Loomis L. D., Michael N. L., Nara P. L., Birx D. L. Differential role of V3-specific antibodies in neutralization assays involving primary and laboratory-adapted isolates of HIV type 1. AIDS Res Hum Retroviruses. 1995 Nov;11(11):1379–1391. doi: 10.1089/aid.1995.11.1379. [DOI] [PubMed] [Google Scholar]
- Vogel T., Kurth R., Norley S. The majority of neutralizing Abs in HIV-1-infected patients recognize linear V3 loop sequences. Studies using HIV-1MN multiple antigenic peptides. J Immunol. 1994 Aug 15;153(4):1895–1904. [PubMed] [Google Scholar]
- Weber J. N., Clapham P. R., Weiss R. A., Parker D., Roberts C., Duncan J., Weller I., Carne C., Tedder R. S., Pinching A. J. Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis. Lancet. 1987 Jan 17;1(8525):119–122. doi: 10.1016/s0140-6736(87)91964-7. [DOI] [PubMed] [Google Scholar]
- Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
- Weiss R. A., Clapham P. R., Cheingsong-Popov R., Dalgleish A. G., Carne C. A., Weller I. V., Tedder R. S. Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature. 1985 Jul 4;316(6023):69–72. doi: 10.1038/316069a0. [DOI] [PubMed] [Google Scholar]
- Wrin T., Crawford L., Sawyer L., Weber P., Sheppard H. W., Hanson C. V. Neutralizing antibody responses to autologous and heterologous isolates of human immunodeficiency virus. J Acquir Immune Defic Syndr. 1994 Mar;7(3):211–219. [PubMed] [Google Scholar]
- Wrin T., Loh T. P., Vennari J. C., Schuitemaker H., Nunberg J. H. Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera. J Virol. 1995 Jan;69(1):39–48. doi: 10.1128/jvi.69.1.39-48.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhang L. Q., MacKenzie P., Cleland A., Holmes E. C., Brown A. J., Simmonds P. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J Virol. 1993 Jun;67(6):3345–3356. doi: 10.1128/jvi.67.6.3345-3356.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhang L., Huang Y., He T., Cao Y., Ho D. D. HIV-1 subtype and second-receptor use. Nature. 1996 Oct 31;383(6603):768–768. doi: 10.1038/383768a0. [DOI] [PubMed] [Google Scholar]
- Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993 Aug 27;261(5125):1179–1181. doi: 10.1126/science.8356453. [DOI] [PubMed] [Google Scholar]
- Zhu T., Wang N., Carr A., Nam D. S., Moor-Jankowski R., Cooper D. A., Ho D. D. Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission. J Virol. 1996 May;70(5):3098–3107. doi: 10.1128/jvi.70.5.3098-3107.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zolla-Pazner S., Sharpe S. A resting cell assay for improved detection of antibody-mediated neutralization of HIV type 1 primary isolates. AIDS Res Hum Retroviruses. 1995 Dec;11(12):1449–1458. doi: 10.1089/aid.1995.11.1449. [DOI] [PubMed] [Google Scholar]
- Zwart G., Back N. K., Ramautarsing C., Valk M., van der Hoek L., Goudsmit J. Frequent and early HIV-1MN neutralizing capacity in sera from Dutch HIV-1 seroconverters is related to antibody reactivity to peptides from the gp120 V3 domain. AIDS Res Hum Retroviruses. 1994 Mar;10(3):245–251. doi: 10.1089/aid.1994.10.245. [DOI] [PubMed] [Google Scholar]
- Zwart G., van der Hoek L., Valk M., Cornelissen M. T., Baan E., Dekker J., Koot M., Kuiken C. L., Goudsmit J. Antibody responses to HIV-1 envelope and gag epitopes in HIV-1 seroconverters with rapid versus slow disease progression. Virology. 1994 Jun;201(2):285–293. doi: 10.1006/viro.1994.1293. [DOI] [PubMed] [Google Scholar]